Beyond Bisphosphonates - New Osteoporosis Medications Under Research: Denosumab and Protelos
For those dissatisfied with current drug options for treating osteoporosis: a new medication being developed by Amgen may be making headway toward the U.S. market. Denosumab, as it is called, would be taken by injection twice a year. The drug inhibits bone remodeling by binding to and thereby blocking the function of a protein known as nuclear factor kappa B ligand (RANKL), which mediates the production and activation of osteoclasts. Osteoclasts are the cells that break down bones, and the same ones targeted by bisphosphonate medication.
"The effect is the same as a bisphosphonate, but through an entirely different method," explains Dr. Recker, chief of the Endocrinology Division at Creighton University Medical Center's Osteoporosis Research Center, who is optimistic that this drug will reach the market.
Less Stomach Irritation from Osteoporosis Treatment?: No Known Esophageal Side Effects for Denosumab
Dr. Recker, who is also vice president of the National Osteoporosis Foundation, points out that denosumab doesn't accumulate in the body and has no known esophageal side effects. "It has a good safety profile," he says.
So far a number of research efforts have indicated that this medicine may substantially increase bone density. A major study comparing the effects on bone mineral density of denosumab head-to-head with Fosamax is due this year, as well as an even larger study focusing primarily on vertebral fractures. After that research is complete Amgen may file for FDA approval.
Another osteoporosis drug you may have heard of - but probably haven't taken, unless you've spent some time abroad - is strontium ranelate, sold under the name Protelos in Europe. The medication, manufactured by French company Servier, is based on a mineral originally discovered in lead mines in Scotland. The drug is not currently approved by the FDA for use in the United States, but is used widely in Western Europe, Australia and other parts of the world.
The medicine works by simultaneously increasing bone formation and reducing the bone resorption process, according to the manufacturer. Two major studies appear to indicate a reduction in fractures - particularly vertebral fractures - for postmenopausal women taking the drug. The usual dosage is 2 grams of powder taken daily, dissolved in a glass of water at bedtime. Unlike bisphosphonates, one can lie down immediately after taking this medicine.
While the medicine is usually well tolerated and severe side effects are rare, some doctors question its efficacy. Dr. Recker, for example, says he is not convinced by the claims of the manufacturer of the medicine's anabolic capacities.
According to a recent article in the New England Journal of Medicine, bone biopsies of strontium ranelate patients show less bone resorption but no evidence of increased bone formation. Bone density is increased, however, because the substance is incorporated into the bone mineral.
Dr. Recker points out that effect is misleading because the mineral is denser than the calcium normally found in the skeleton. "It's hard to tell if there's an actual increase in bone," in the patient, says Dr. Recker, who is doubtful the medication will gain approval for use in the U.S.
Interestingly, an American-based company, Osteologix, recently announced favorable results in a clinical trial for its investigational drug strontium malonate, known as NB S101. Like Protelos, NB S101 also incorporates strontium, but it is used with malonic acid rather than the ranelic acid of the European medication. The studies indicated the Osteologix drug increased bone mineral density in the lumbar spine, at levels about equivalent to strontium ranelate. In addition, the drug helped patients reduce CTX-1, a biomarker associated with bone resorption activity, at greater levels than those taking Protelos. Unlike the powder form of the European drug, however, strontium malonate is being formulated as a tablet to be taken once daily.